Effects of Parathyroid Hormone on Hepatocyte pHi and Na+-H+ Exchanger Activity
| Autor: | Atul Sahai, Mariusz Klin, Miroslaw Smogorzewski, Maria Michnowska, Shaul G. Massry |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Calcium metabolism
medicine.medical_specialty Voltage-dependent calcium channel business.industry Antiporter Intracellular pH Parathyroid hormone Amiloride Sodium–hydrogen antiporter Endocrinology Nephrology Internal medicine Medicine business hormones hormone substitutes and hormone antagonists Protein kinase C medicine.drug |
| Zdroj: | American Journal of Nephrology. 16:431-441 |
| ISSN: | 1421-9670 0250-8095 |
| Popis: | Parathyroid hormone (PTH) induces a rise in cytosolic calcium--[Ca2+]i--in many cells. A rise in [Ca2+]i activates the Na(+)-H+ antiport, but PTH inhibits the Na(+)-H+ exchanger in kidney cells. Since PTH induces a rise in [Ca2+]i of hepatocytes, we examined the effect of PTH on their Na(+)-H+ antiport and intracellular pH(pHi). PTH caused an initial activation of Na(+)-H+ exchanger, and this stimulation is amiloride sensitive. The activation of the Na(+)-H+ exchanger was followed by progressive inhibition. This inhibitory effect was dose dependent and occurred over a wide range of external sodium concentrations. PTH also caused a progressive rise in hepatocyte pHi which became apparent after the initial activation of the Na(+)-H+ antiport. This alkalinization of hepatocytes occurred when the cells were placed in sodium or potassium media. These actions of PTH were mimicked by dibutyryl cyclic AMP and 12-o-tetradecanoylphorbol-13-acetate(TPA) and were abolished by H-89 (an inhibitor of protein kinase A), staurosporine (an inhibitor of protein kinase C), and the calcium channel blockers verapamil or nifedipine. The data are consistent with the formulation that PTH, through the activation of the cAMP-protein kinase A pathway, protein kinase C, and calcium channels inhibitable by verapamil or nifedipine, induces a rise in [Ca2+]i of hepatocytes. The latter event causes an initial activation of Na(+)-H+ antiport which is followed by a rise in pHi. Also, PTH may facilitate a Ca2+/2H+ exchange across the hepatocyte membrane and causes an initial and persistent rise in pHi, since the rise in pHi occurred under conditions where Na(+)-H+ antiport is inactive (potassium media). In addition, PTH either directly or through activation of second messenger(s) leads to an increased ammonia content of hepatocytes which could maintain a high pHi. Consequently, the Na(+)-H+ antiport is inhibited in an effort to restore the pHi back to normal. |
| Databáze: | OpenAIRE |
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